Coutanceau Bérangère, Dos Santos Esther, Swierkowski Blanchard Nelly, Sanchez Louboutin Anne, Boitrelle Florence, Margueritte François, Vialard François, Serazin Valérie, Fathallah Khadija
Department of Obstetrics and Gynaecology, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, France.
Medical Biology Laboratory, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, France.
Biomedicines. 2023 Mar 7;11(3):817. doi: 10.3390/biomedicines11030817.
Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today's approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide.
反复胚胎植入失败（RIF）对患者和临床医生来说都是困扰和沮丧的根源。如今治疗RIF的方法大多是经验性的，效果有限。RIF的主要原因是子宫内膜容受性差和胚胎质量不佳。最近的研究表明，由于辅助性T细胞（Th）1和Th2细胞因子失衡导致免疫失调参与其中；这为治疗RIF女性并提高植入率开辟了新视角。我们进行了一项干预性、纵向、前瞻性队列研究，以探讨纠正细胞因子失衡对RIF女性临床妊娠率的影响。77名RIF女性在植入窗期接受了子宫内膜活检。通过研究子宫自然杀伤（uNK）细胞的活化和成熟、IL-15/Fn-14 mRNA比值（uNK活化/成熟的生物标志物）以及IL-18/TWEAK mRNA比值（血管生成和Th1/Th2平衡的标志物）来评估细胞因子谱。对子宫内膜细胞因子谱异常（过度活化或活化不足）的女性开始进行个性化治疗。我们记录了后续胚胎移植后的临床妊娠率。总体而言，72.7%（56/77）的患者子宫内膜细胞因子谱异常（68.8%（n = 53）为过度活化，3.9%（n = 3）为活化不足）。根据子宫内膜情况进行治疗（或不治疗）后，总体临床妊娠率为30.2%。我们的结果表明，尽管分析的病例数较少，但适当治疗对RIF女性的持续妊娠率可能有积极影响。现在必须在有大量特征明确患者的随机研究中验证这些结果。通过应用先前发表的决策树，这种治疗方法可在全球范围内的诊所实施。
